Mouse Hepatitis (MHV) has been reproduced experimentally in nu/nu mice by experimental infection (mortality 5-7 days) and by cohabitation with experimentally MHV infected CD-1 mice (mortality 40-50 days). Disease free CD-1 mice seroconverted to MHV when cohabited with naturally infected B6C3F1 mice. MHV is shed in the feces of naturally infected B6C3F1 mice and the disease can be transmitted to MHV free CD-1 mice by direct fecal exposure. CD-1 and nude mice can be experimentally infected by the intra-nasal (i.n.), intraperitoneal (i.p.), oral or gavage (stomach) routes. ELISA optical density (O.D.) values in CD-1 mice at 19 days post MHV-infection by these routes were: i.n. (0.27, 0.10, and 0.12), i.p. (1.47 and 1.00), oral (1.21, 0.89, and 1.50), and gavage (0.47 and 0.00). ELISA O.D. values 0.17 and higher are considered positive in serological screening results. ELISA O.D. values were more uniform and higher in mice infected by the oral and i.p. routes. Intra-nasal and gavage exposure produced variable results.